Siwetz Monika, Sundl Monika, Kolb Dagmar, Hiden Ursula, Herse Florian, Huppertz Berthold, Gauster Martin
Institute of Cell Biology, Histology and Embryology, Medical University Graz, Harrachgasse 21/VII, 8010, Graz, Austria.
Histochem Cell Biol. 2015 Jun;143(6):565-74. doi: 10.1007/s00418-014-1304-0. Epub 2015 Jan 8.
The chemokine fractalkine (CX3CL1) recently attracted increasing attention in the field of placenta research due to its dual nature, acting both as membrane-bound and soluble forms. While the membrane-bound form mediates flow-resistant adhesion of leukocytes to endothelial and epithelial cells via its corresponding receptor CX3CR1, the soluble form arises from metalloprotease-dependent shedding and bears chemoattractive activity for monocytes, natural killer cells and T cells. In human placenta, fractalkine is expressed at the apical microvillous plasma membrane of the syncytiotrophoblast, which may enable close physical contact with circulating maternal leukocytes. Based on these observations, we tested the hypothesis that fractalkine mediates adhesion of monocytes to the villous trophoblast. Forskolin-induced differentiation and syncytialization of the trophoblast cell line BeWo was accompanied with a substantial upregulation in fractalkine expression and led to increased adhesion of the monocyte cell line THP-1, which preferentially bound to syncytia. Blocking as well as silencing of the fractalkine receptor CX3CR1 proved involvement of the fractalkine/CX3CR1 system in adherence of THP-1 monocytes to villous trophoblast. Pre-incubation of THP-1 monocytes with human recombinant fractalkine as well as silencing of CX3CR1 expression in THP-1 monocytes significantly impaired their adherence to BeWo cells and primary term trophoblasts. The present study suggests fractalkine as another candidate among the panel of adhesion molecules enabling stable interaction between leukocytes and the syncytiotrophoblast.
趋化因子fractalkine（CX3CL1）因其兼具膜结合形式和可溶性形式的双重特性，最近在胎盘研究领域受到越来越多的关注。膜结合形式通过其相应受体CX3CR1介导白细胞与内皮细胞和上皮细胞的抗流黏附，而可溶性形式则源于金属蛋白酶依赖性脱落，对单核细胞、自然杀伤细胞和T细胞具有趋化活性。在人胎盘中，fractalkine表达于合体滋养层细胞顶端微绒毛质膜，这可能使其能够与循环中的母体白细胞进行紧密的物理接触。基于这些观察结果，我们检验了fractalkine介导单核细胞与绒毛滋养层细胞黏附的假说。佛司可林诱导滋养层细胞系BeWo分化和融合，同时fractalkine表达显著上调，并导致单核细胞系THP-1的黏附增加，THP-1优先与合体细胞结合。阻断以及沉默fractalkine受体CX3CR1证明了fractalkine/CX3CR1系统参与THP-1单核细胞与绒毛滋养层细胞的黏附。用重组人fractalkine预孵育THP-1单核细胞以及沉默THP-1单核细胞中CX3CR1的表达，均显著削弱了它们与BeWo细胞和足月原代滋养层细胞的黏附。本研究表明，fractalkine是使白细胞与合体滋养层细胞之间实现稳定相互作用的黏附分子组中的另一个候选分子。
